tbuckley/cabot-search huggingface dataset:
Real-World Treatment Patterns in Patients With HER2-Amplified Metastatic Colorectal Cancer: A Clinical-Genomic Database Study
Authors: John H. Strickler, Ling-I Hsu, Phoebe Wright, Michael Stecher, Muriel F. Siadak, Maria Corinna Palanca-Wessels, Junhua Yu, Nicole Zhang, Carin R. Espenschied, Kathryn Lang, Tanios S. Bekaii-Saab
Journal: Journal of the National Comprehensive Cancer Network (2023)

Background: HER2 amplification (HER2+) occurs in approximately 3% of patients with metastatic colorectal cancer (mCRC). Despite the recent addition of HER2-directed therapies to treatment recommendations in the NCCN Guidelines, until more recently there were no FDA-approved treatments. This study examined real-world treatment patterns in patients with HER2+ mCRC in the United States before and after the emerging awareness of HER2-directed therapies in 2018. Methods: This was a retrospective observational study of patients with HER2+ mCRC from the GuardantINFORM database, which contains claims data for patients with Guardant360 genomic testing results. Patients were aged ≥18 years, were diagnosed with mCRC between January 2014 and September 2020, and had confirmed ERBB2 amplification via the blood-based Guardant360 test. Treatment patterns and real-world time to next treatment (rwTTNT) were evaluated. Results: This study included 142 patients with a median age of 59 years; 31 (21.8%) patients with ERBB2 amplifications also had ERBB2 mutations. Treatment patterns were heterogeneous and evolved over time; before 2018, the most common regimen prescribed after detection of ERBB2 amplification was anti-VEGF therapy with or without chemotherapy (31.6%; n=25), and after 2018, HER2-directed therapies were the most commonly prescribed (36.5%; n=23). Median rwTTNT among the overall cohort was 8.4 months (95% CI, 6.5–10.0); rwTTNT was numerically longer in patients who received HER2-directed therapy compared with those who received non–HER2-directed therapies (11.0 months [95% CI, 6.3–12.3] vs 7.2 months [95% CI, 5.8–9.6]). Conclusions: This real-world study of the largest clinically annotated dataset of patients with HER2+ mCRC showed that many patients do not receive HER2-directed therapy despite its inclusion in NCCN Guidelines, with heterogeneous treatment patterns suggesting that standard of care remains undefined and targeted therapy remains underutilized. Greater awareness of the unmet need in this patient population, together with new effective therapies, will facilitate strategies for improved, targeted treatment approaches.
Subcutaneous Implantable Cardioverter-Defibrillators in Patients With Congenital Heart Disease
Authors: Victor Waldmann, Christelle Marquié, Francis Bessière, David Perrot, Frédéric Anselme, Nicolas Badenco, Sergio Barra, Géraldine Bertaux, Hugues Blangy, Pierre Bordachar, Serge Boveda, Michel Chauvin, Nicolas Clémenty, Gaël Clerici, Nicolas Combes, Pascal Defaye, Jean-Claude Deharo, Philippe Durand, Guillaume Duthoit, Romain Eschalier, Laurent Fauchier, Rodrigue Garcia, Olivier Geoffroy, Edouard Gitenay, Jean-Baptiste Gourraud, Charles Guenancia, Laurence Iserin, Peggy Jacon, Laurence Jesel-Morel, Fawzi Kerkouri, Didier Klug, Linda Koutbi, Fabien Labombarda, Magalie Ladouceur, Gabriel Laurent, Christophe Leclercq, Baptiste Maille, Alice Maltret, Grégoire Massoulié, Pierre Mondoly, Sandro Ninni, Pierre Ollitrault, Jean-Luc Pasquié, Bertrand Pierre, Pénélope Pujadas, Laure Champ-Rigot, Frédéric Sacher, Nicolas Sadoul, Alexandre Schatz, Pierre Winum, Paul-Ursmar Milliez, Vincent Probst, Eloi Marijon
Journal: Journal of the American College of Cardiology (2023)
Annals Graphic Medicine - Preparing for a Genomic Future
Authors: Courtney J. Smith, Brian R. Smith
Journal: Annals of Internal Medicine (2023)

Web Exclusives8 August 2023Annals Graphic Medicine - Preparing for a Genomic FutureFREECourtney J. Smith, and Brian R. SmithCourtney J. SmithStanford University School of Medicine, Stanford, California (C.J.S., B.R.S.)Search for more papers by this author, and Brian R. SmithStanford University School of Medicine, Stanford, California (C.J.S., B.R.S.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/G22-0055 SectionsAboutVisual AbstractPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Download figure Download PowerPoint Download figure Download PowerPoint Download figure Download PowerPoint Download figure Download PowerPoint Comments0 CommentsSign In to Submit A Comment Author, Article, and Disclosure InformationAuthors: Courtney J. Smith; Brian R. SmithAffiliations: Stanford University School of Medicine, Stanford, California (C.J.S., B.R.S.)Disclosures: Authors have reported no disclosures of interest. Forms can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=G22-0055.Author/Illustrator Information: Courtney J. Smith is a Genetics MD/PhD student at Stanford (e-mail, [email protected].edu). Brian R. Smith is an MD student at Stanford (e-mail, [email protected].edu). Both authors contributed equally to this work.This article was published at Annals.org on 8 August 2023. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Latest ePublished: 8 August 2023 Copyright & PermissionsCopyright © 2023 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Association between particulate matter (PM)2·5 air pollution and clinical antibiotic resistance: a global analysis
Authors: Zhenchao Zhou, Xinyi Shuai, Zejun Lin, Xi Yu, Xiaoliang Ba, Mark A Holmes, Yonghong Xiao, Baojing Gu, Hong Chen
Journal: The Lancet Planetary Health (2023)

Antibiotic resistance is an increasing global issue, causing millions of deaths worldwide every year. Particulate matter (PM)2·5 has diverse elements of antibiotic resistance that increase its spread after inhalation. However, understanding of the contribution of PM2·5 to global antibiotic resistance is poor. Through univariate and multivariable analysis, we aimed to present the first global estimates of antibiotic resistance and burden of premature deaths attributable to antibiotic resistance resulting from PM2·5 pollution.For this global analysis, data on multiple potential predictors (ie, air pollution, antibiotic use, sanitation services, economics, health expenditure, population, education, climate, year, and region) were collected in 116 countries from 2000 to 2018 to estimate the effect of PM2·5 on antibiotic resistance via univariate and multivariable analysis. Data were obtained from ResistanceMap, European Centre for Disease Prevention and Control Surveillance Atlas (antimicrobial-resistance sources), and PLISA Health Information Platform for the Americas. Future global aggregate antibiotic resistance and premature mortality trends derived from PM2·5 in different scenarios (eg, 50% reduced antibiotic use or PM2·5 controlled to 5 μg/m3) were projected until 2050.The final dataset included more than 11·5 million tested isolates. Raw antibiotic-resistance data included nine pathogens and 43 types of antibiotic agents. Significant correlations between PM2·5 and antibiotic resistance were consistent globally in most antibiotic-resistant bacteria (R2=0·42-0·76, p<0·0001), and correlations have strengthened over time. Antibiotic resistance derived from PM2·5 caused an estimated 0·48 (95% CI 0·34-0·60) million premature deaths and 18·2 (13·4-23·0) million years of life lost in 2018 worldwide, corresponding to an annual welfare loss of US$395 (290-500) billion due to premature deaths. The 5 μg/m3 target of concentration of PM2·5 in the air quality guidelines set by WHO, if reached in 2050, was estimated to reduce antibiotic resistance by 16·8% (95% CI 15·3-18·3) and avoid 23·4% (21·2-25·6) of premature deaths attributable to antibiotic resistance, equivalent to a saving of $640 (580-671) billion.This analysis is the first to describe the association between PM2·5 and clinical antibiotic resistance globally. Results provide new pathways for antibiotic-resistance control from an environmental perspective.National Natural Science Foundation of China, Fundamental Research Funds for the Central Universities, Zhejiang University Global Partnership Fund, and China Postdoctoral Science Foundation.
Blind spots obscure understanding of how forests affect human health
Authors: Todd S Rosenstock, Dominic Rowland, Zara Liew, Katie Hickson, Lilly Zeitler, Stepha McMullin, Ramni Jamnadass, Amy Ickowitz
Journal: The Lancet Planetary Health (2023)

Health crises have raised awareness of the links between forests and human health. For example, outbreaks of Ebola virus and hypotheses about the origins of SARS-CoV-2 have highlighted the risk of zoonotic spillover events from forest-dwelling animals.1,2 Likewise, forest fires in Australia (2019–20), the Amazon rainforest (2019), and southeast Asia (2015) have drawn attention to the respiratory health effects on populations exposed to smoke and haze.3 Other links between forests and health, such as the role of forests in mitigating natural disasters4 and regulating infectious disease vectors,5 are well established but less well known outside the scientific community.
Non-target effects of chemical malaria vector control on other biological and mechanical infectious disease vectors
Authors: Ndey Bassin Jobe, Silvie Huijben, Krijn P Paaijmans
Journal: The Lancet Planetary Health (2023)

Public health insecticides play a crucial role in malaria control and elimination programmes. Many other arthropods, including mechanical and biological vectors of infectious diseases, have similar indoor feeding or resting behaviours, or both, as malaria mosquitoes, and could be exposed to the same insecticides. In this Personal View, we show that little is known about the insecticide susceptibility status and the extent of exposure to malaria interventions of other arthropod species. We highlight that there is an urgent need to better understand the selection pressure for insecticide resistance in those vectors, to ensure current and future active ingredients remain effective in targeting a broad range of arthropod species, allowing us to prevent and control future outbreaks of infectious diseases other than malaria.
The NRF2/Keap1 pathway as a therapeutic target in inflammatory bowel disease
Authors: Sem Geertsema, Arno R. Bourgonje, Raphael R. Fagundes, Ranko Gacesa, Rinse K. Weersma, Harry van Goor, Giovanni E. Mann, Gerard Dijkstra, Klaas N. Faber
Journal: Trends in Molecular Medicine (2023)
Device-based measurement of physical activity in cardiovascular healthcare: possibilities and challenges
Authors: Timothy James Chico, Emmanuel Stamatakis, Fabio Ciravegna, Jessilyn Dunn, Simon Redwood, Rasha Al-lamee, Reecha Sofat, Jason Gill
Journal: British Journal of Sports Medicine (2023)

Low physical activity 1 and slow walking pace 2 have a two-way relationship with cardiovascular disease (CVD).Low physical activity increases future risk of CVD, while when CVD develops it often impairs activity.This means that wearable or smartphone-based measurement of physical activity may provide clinically useful "digital biomarkers".Clinicians predict future risk, diagnose disease, and recommend appropriate treatment, and for any biomarker to be used in healthcare, its measurement must influence these decisions to improve patient outcomes.Here we consider how this may be achieved.
Youth activists' perspectives on climate, sexual and reproductive health and rights, and gender inequality
Authors: Victória Miguel Rampazzo, Anne Heloise Barbosa do Nascimento, Shakira Choonara, Rosalind Helfand
Journal: The Lancet Planetary Health (2023)

Generation Equality is a global multistakeholder partnership mechanism advocating for a wide range of issues, including the gender and climate justice agenda. Convened by UN Women in 2020, Generation Equality is based on the landmark 25th anniversary of the 1995 Beijing Declaration and Platform for Action on the promotion of women's rights. In this Comment, we build on a Generation Equality side event held during the Sixty-Sixth Commission on the Status of Women in 2021, which placed a spotlight on the neglected but highly interconnected climate, sexual and reproductive health and rights (SRHR), and gender inequality crises.
Heatwaves and wildfires suffocate our healthy start to life: time to assess impact and take action
Authors: Amita Bansal, Nicolas Cherbuin, Deborah L Davis, Michael J Peek, Amanda Wingett, Bruce K Christensen, Hazel Carlisle, Margaret Broom, Danielle A J M Schoenaker, Jane E Dahlstrom, Christine B Phillips, Sotiris Vardoulakis, Ralph Nanan, Christopher J Nolan
Journal: The Lancet Planetary Health (2023)

Adverse environmental exposures in utero and early childhood are known to programme long-term health. Climate change, by contributing to severe heatwaves, wildfires, and other natural disasters, is plausibly associated with adverse pregnancy outcomes and an increase in the future burden of chronic diseases in both mothers and their babies. In this Personal View, we highlight the limitations of existing evidence, specifically on the effects of severe heatwave and wildfire events, and compounding syndemic events such as the COVID-19 pandemic, on the short-term and long-term physical and mental health of pregnant women and their babies, taking into account the interactions with individual and community vulnerabilities. We highlight a need for an international, interdisciplinary collaborative effort to systematically study the effects of severe climate-related environmental crises on maternal and child health. This will enable informed changes to public health policy and clinical practice necessary to safeguard the health and wellbeing of current and future generations.
Setbacks in the quest for universal health coverage in Mexico: polarised politics, policy upheaval, and pandemic disruption
Authors: Felicia Marie Knaul, Hector Arreola-Ornelas, Michael Touchton, Tim McDonald, Merike Blofield, Leticia Avila Burgos, Octavio Gómez-Dantés, Pablo Kuri, Adolfo Martinez-Valle, Oscar Méndez-Carniado, Renu Sara Nargund, Thalia Porteny, Sandra Gabriela Sosa-Rubí, Edson Serván-Mori, Maya Symes, Valentina Vargas Enciso, Julio Frenk
Journal: The Lancet (2023)
The effectiveness of exercise and physical activity programs on fatigue and sleep in people with arthritis – A systematic review with meta-analysis
Authors: N. Runge, A. Arribas-Romano, C. Labie, O. Mairesse, Z. Goossens, J. Nijs, A. Malfliet, S. Verschueren, D. Van Assche, K. de Vlam, L. De Baets
Journal: Sleep Medicine Reviews (2023)
Author correction to “Neutralization of SARS-CoV-2 pseudovirus using ACE2-engineered extracellular vesicles” [Acta Pharmaceutica Sinica B 12 (2022) 1523–1533]
Authors: Canhao Wu, Qin Xu, Huiyuan Wang, Bin Tu, Jiaxin Zeng, Pengfei Zhao, Mingjie Shi, Hong Qiu, Yongzhuo Huang
Journal: Acta Pharmaceutica Sinica B (2023)

[This corrects the article DOI: 10.1016/j.apsb.2021.09.004.].
Activation of PXR causes drug interactions with Paxlovid in transgenic mice
Authors: Saifei Lei, Alice Guo, Jie Lu, Qian Qi, Aaron S. Devanathan, Junjie Zhu, Xiaochao Ma
Journal: Acta Pharmaceutica Sinica B (2023)

Paxlovid is a nirmatrelvir (NMV) and ritonavir (RTV) co-packaged medication used for the treatment of coronavirus disease 2019 (COVID-19). The active component of Paxlovid is NMV and RTV is a pharmacokinetic booster. Our work aimed to investigate the drug/herb-drug interactions associated with Paxlovid and provide mechanism-based guidance for the clinical use of Paxlovid. By using recombinant human cytochrome P450s (CYPs), we confirmed that CYP3A4 and 3A5 are the major enzymes responsible for NMV metabolism. The role of CYP3A in Paxlovid metabolism were further verified in Cyp3a-null mice, which showed that the deficiency of CYP3A significantly suppressed the metabolism of NMV and RTV. Pregnane X receptor (PXR) is a ligand-dependent transcription factor that upregulates CYP3A4/5 expression. We next explored the impact of drug- and herb-mediated PXR activation on Paxlovid metabolism in a transgenic mouse model expressing human PXR and CYP3A4/5. We found that PXR activation increased CYP3A4/5 expression, accelerated NMV metabolism, and reduced the systemic exposure of NMV. In summary, our work demonstrated that PXR activation can cause drug interactions with Paxlovid, suggesting that PXR-activating drugs and herbs should be used cautiously in COVID-19 patients receiving Paxlovid.
EULAR recommendations for the use of imaging in large vessel vasculitis in clinical practice: 2023 update
Authors: Christian Dejaco, Sofia Ramiro, Milena Bond, Philipp Bosch, Cristina Ponte, Sarah Louise Mackie, Thorsten A Bley, Daniel Blockmans, Sara Brolin, Ertugrul Cagri Bolek, Rebecca Cassie, Maria C Cid, Juan Molina-Collada, Bhaskar Dasgupta, Berit Dalsgaard Nielsen, Eugenio De Miguel, Haner Direskeneli, Christina Duftner, Alojzija Hočevar, Anna Molto, Valentin Sebastian Schäfer, Luca Seitz, Riemer H J A Slart, Wolfgang A Schmidt
Journal: Annals of the Rheumatic Diseases (2023)

Objectives To update the EULAR recommendations for the use of imaging modalities in primary large vessel vasculitis (LVV). Methods A systematic literature review update was performed to retrieve new evidence on ultrasound, MRI, CT and [ 18 F]-fluorodeoxyglucose positron emission tomography (FDG-PET) for diagnosis, monitoring and outcome prediction in LVV. The task force consisted of 24 physicians, health professionals and patients from 14 countries. The recommendations were updated based on evidence and expert opinion, iterating until voting indicated consensus. The level of agreement was determined by anonymous votes. Results Three overarching principles and eight recommendations were agreed. Compared to the 2018 version, ultrasound is now recommended as first-line imaging test in all patients with suspected giant cell arteritis, and axillary arteries should be included in the standard examination. As an alternative to ultrasound, cranial and extracranial arteries can be examined by FDG-PET or MRI. For Takayasu arteritis, MRI is the preferred imaging modality; FDG-PET, CT or ultrasound are alternatives. Although imaging is not routinely recommended for follow-up, ultrasound, FDG-PET or MRI may be used for assessing vessel abnormalities in LVV patients with suspected relapse, particularly when laboratory markers of inflammation are unreliable. MR-angiography, CT-angiography or ultrasound may be used for long-term monitoring of structural damage, particularly at sites of preceding vascular inflammation. Conclusions The 2023 EULAR recommendations provide up-to-date guidance for the role of imaging in the diagnosis and assessment of patients with LVV.
Cartilage-specific<i>Sirt6</i>deficiency represses IGF-1 and enhances osteoarthritis severity in mice
Authors: John A Collins, C James Kim, Ashley Coleman, Abreah Little, Matheus M Perez, Emily J Clarke, Brian Diekman, Mandy J Peffers, Susanna Chubinskaya, Ryan E Tomlinson, Theresa A Freeman, Richard F Loeser
Journal: Annals of the Rheumatic Diseases (2023)

Prior studies noted that chondrocyte SIRT6 activity is repressed in older chondrocytes rendering cells susceptible to catabolic signalling events implicated in osteoarthritis (OA). This study aimed to define the effect of
From clinical variables to multiomics analysis: a margin morphology-based gross classification system for hepatocellular carcinoma stratification
Authors: Zhongqi Fan, Meishan Jin, Lei Zhang, Nanya Wang, Mingyue Li, Chuanlei Wang, Feng Wei, Ping Zhang, Xiaohong Du, Xiaodong Sun, Wei Qiu, Meng Wang, Hongbin Wang, Xiaoju Shi, Junfeng Ye, Chao Jiang, Jianpeng Zhou, Wengang Chai, Jun Qi, Ting Li, Ruoyan Zhang, Xingkai Liu, Bo Huang, Kaiyuan Chai, Yannan Cao, Wentao Mu, Yu Huang, Tian Yang, Huimao Zhang, Limei Qu, Yahui Liu, Guangyi Wang, Guoyue Lv
Journal: Gut (2023)

Selecting interventions for patients with solitary hepatocellular carcinoma (HCC) remains a challenge. Despite gross classification being proposed as a potential prognostic predictor, its widespread use has been restricted due to inadequate studies with sufficient patient numbers and the lack of established mechanisms. We sought to investigate the prognostic impacts on patients with HCC of different gross subtypes and assess their corresponding molecular landscapes.A prospective cohort of 400 patients who underwent hepatic resection for solitary HCC was reviewed and analysed and gross classification was assessed. Multiomics analyses were performed on tumours and non-tumour tissues from 49 patients to investigate the mechanisms underlying gross classification. Inverse probability of treatment weight (IPTW) was used to control for confounding factors.Overall 3-year survival rates varied significantly among the four gross subtypes (type I: 91%, type II: 80%, type III: 74.6%, type IV: 38.8%). Type IV was found to be independently associated with poor prognosis in both the entire cohort and the IPTW cohort. The four gross subtypes exhibited three distinct transcriptional modules. Particularly, type IV tumours exhibited increased angiogenesis and immune score as well as decreased metabolic pathways, together with highest frequency of TP53 mutations. Patients with type IV HCC may benefit from adjuvant intra-arterial therapy other than the other three subtypes. Accordingly, a modified trichotomous margin morphological gross classification was established.Different gross types of HCC showed significantly different prognosis and molecular characteristics. Gross classification may aid in development of precise individualised diagnosis and treatment strategies for HCC.
Clinical care pathway to detect advanced liver disease in patients with type 2 diabetes through automated fibrosis score calculation and electronic reminder messages: a randomised controlled trial
Authors: Xinrong Zhang, Terry Cheuk-Fung Yip, Grace Lai-Hung Wong, Wei-Xuan Leow, Lilian Yan Liang, Lee-Ling Lim, Guanlin Li, Luqman Ibrahim, Huapeng Lin, Jimmy Che To Lai, Angel Mei-Ling Chim, Henry Lik Yuen Chan, Alice Pik-Shan Kong, Wah Kheong Chan, Vincent Wai-Sun Wong
Journal: Gut (2023)

We aimed to test the hypothesis that automated fibrosis score calculation and electronic reminder messages could increase the detection of advanced liver disease in patients with type 2 diabetes.